AI Article Synopsis
- * Through whole exome sequencing and gene analysis of tumors and patient-derived xenografts, researchers found that Polo-like kinase 1 (PLK1) is significantly up-regulated and linked to poor treatment outcomes.
- * PLK1 inhibition not only reduces tumor size in resistant breast cancer models but also indicates a potential new treatment pathway for patients who do not respond to current therapies like palbociclib and anastrozole.
Article Abstract
A significant proportion of patients with oestrogen receptor (ER) positive breast cancers (BC) develop resistance to endocrine treatments (ET) and relapse with metastatic disease. Here we perform whole exome sequencing and gene expression analysis of matched primary breast tumours and bone metastasis-derived patient-derived xenografts (PDX). Transcriptomic analyses reveal enrichment of the G2/M checkpoint and up-regulation of Polo-like kinase 1 (PLK1) in PDX. PLK1 inhibition results in tumour shrinkage in highly proliferating CCND1-driven PDX, including different RB-positive PDX with acquired palbociclib resistance. Mechanistic studies in endocrine resistant cell lines, suggest an ER-independent function of PLK1 in regulating cell proliferation. Finally, in two independent clinical cohorts of ER positive BC, we find a strong association between high expression of PLK1 and a shorter metastases-free survival and poor response to anastrozole. In conclusion, our findings support clinical development of PLK1 inhibitors in patients with advanced CCND1-driven BC, including patients progressing on palbociclib treatment.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426966 | PMC |
| http://dx.doi.org/10.1038/s41467-020-17697-1 | DOI Listing |
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